The broad objectives of this proposal are to evaluate testicular and accessory sex gland function in a large population of subfertile males. The expertise of an interdepartmental program involving Urology, Endocrinology, Cell Biology and Gynecology affords an in depth evaluation of the pathophysiology of reproductive disorders and the prompt application of new technology. This proposal will correlate the clinical data (history, physical examination, scrotal exploration, testis biopsy and vasography when indicated) with functional measurements of the male reproductive system. To do this, we will (1) analyze seminal quality; (2) assay specific secretory products of the accessory sex glands (carnitine and GPC from the epididymis: fructose from the seminal vesical; and acid phosphatase and citric acid from the prostate); (3) measure serum FSH, LH and testosterone to reflect Sertoli and Leydig cell function; (4) determine if androgen-binding protein can be used as a marker protein in human Sertoli cell function and, if so, assay its concentration in testicular tissue and seminal fluid. The methodology involves the application of conventional and previously only investigational techniques. Serum FSH, LH and testosterone will be determined by RIA. Carnitine will be assayed by gas chromatography, GPC, fructose, acid phosphatase and citric acid by spectrofluorometry. ABP will be measured in human tissue cytosol and in the media of human Sertoli cell cultures using a steady-state polyacrylamide gel electrophoresis system and later by immuno-assay as a specific antibody to ABP becomes available from this laboratory. Using this systematic and quantitative approach to assess reproductive processes in the subfertile male, we plan to identify specific abnormalities of spermatogenesis and accessory sex gland function. It is expected that this will ultimately provide a means for more specific therapeutic intervention.